FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3043103202> ?p ?o ?g. }

• W3043103202 endingPage "612" @default.
• W3043103202 startingPage "601" @default.
• W3043103202 abstract "Idiopathic pulmonary fibrosis is a fatal interstitial lung disease characterized by the TGF-β (transforming growth factor-β)-dependent differentiation of lung fibroblasts into myofibroblasts, which leads to excessive deposition of collagen proteins and progressive scarring. We have previously shown that synthesis of collagen by myofibroblasts requires de novo synthesis of glycine, the most abundant amino acid found in collagen protein. TGF-β upregulates the expression of the enzymes of the de novo serine-glycine synthesis pathway in lung fibroblasts; however, the transcriptional and signaling regulators of this pathway remain incompletely understood. Here, we demonstrate that TGF-β promotes accumulation of ATF4 (activating transcription factor 4), which is required for increased expression of the serine-glycine synthesis pathway enzymes in response to TGF-β. We found that induction of the integrated stress response (ISR) contributes to TGF-β-induced ATF4 activity; however, the primary driver of ATF4 downstream of TGF-β is activation of mTORC1 (mTOR Complex 1). TGF-β activates the PI3K-Akt-mTOR pathway, and inhibition of PI3K prevents activation of downstream signaling and induction of ATF4. Using a panel of mTOR inhibitors, we found that ATF4 activation is dependent on mTORC1, independent of mTORC2. Rapamycin, which incompletely and allosterically inhibits mTORC1, had no effect on TGF-β-mediated induction of ATF4; however, Rapalink-1, which specifically targets the kinase domain of mTORC1, completely inhibited ATF4 induction and metabolic reprogramming downstream of TGF-β. Our results provide insight into the mechanisms of metabolic reprogramming in myofibroblasts and clarify contradictory published findings on the role of mTOR inhibition in myofibroblast differentiation." @default.
• W3043103202 created "2020-07-23" @default.
• W3043103202 creator A5009749327 @default.
• W3043103202 creator A5018496648 @default.
• W3043103202 creator A5030184709 @default.
• W3043103202 creator A5042127182 @default.
• W3043103202 creator A5059656427 @default.
• W3043103202 creator A5064068796 @default.
• W3043103202 creator A5066414145 @default.
• W3043103202 creator A5079814684 @default.
• W3043103202 creator A5080338987 @default.
• W3043103202 creator A5083568219 @default.
• W3043103202 creator A5085995181 @default.
• W3043103202 creator A5087248857 @default.
• W3043103202 date "2020-11-01" @default.
• W3043103202 modified "2023-10-18" @default.
• W3043103202 title "TGF-β Promotes Metabolic Reprogramming in Lung Fibroblasts via mTORC1-dependent ATF4 Activation" @default.
• W3043103202 cites W1589421810 @default.
• W3043103202 cites W1793883704 @default.
• W3043103202 cites W1970194420 @default.
• W3043103202 cites W1972494520 @default.
• W3043103202 cites W1975517035 @default.
• W3043103202 cites W1982219839 @default.
• W3043103202 cites W1999999605 @default.
• W3043103202 cites W2000065998 @default.
• W3043103202 cites W2002583208 @default.
• W3043103202 cites W2019431738 @default.
• W3043103202 cites W2025029681 @default.
• W3043103202 cites W2031938767 @default.
• W3043103202 cites W2035521247 @default.
• W3043103202 cites W2045142779 @default.
• W3043103202 cites W2051522090 @default.
• W3043103202 cites W2056040807 @default.
• W3043103202 cites W2067031028 @default.
• W3043103202 cites W2067298405 @default.
• W3043103202 cites W2074471441 @default.
• W3043103202 cites W2080971278 @default.
• W3043103202 cites W2089783252 @default.
• W3043103202 cites W2098912234 @default.
• W3043103202 cites W2101960743 @default.
• W3043103202 cites W2102298863 @default.
• W3043103202 cites W2109920600 @default.
• W3043103202 cites W2113107987 @default.
• W3043103202 cites W2116043657 @default.
• W3043103202 cites W2120129511 @default.
• W3043103202 cites W2131632095 @default.
• W3043103202 cites W2134106182 @default.
• W3043103202 cites W2134215992 @default.
• W3043103202 cites W2143924572 @default.
• W3043103202 cites W2159731793 @default.
• W3043103202 cites W2169591849 @default.
• W3043103202 cites W2173466127 @default.
• W3043103202 cites W2231149464 @default.
• W3043103202 cites W2258318060 @default.
• W3043103202 cites W2334655995 @default.
• W3043103202 cites W2407198816 @default.
• W3043103202 cites W2565062778 @default.
• W3043103202 cites W2571931234 @default.
• W3043103202 cites W2593816418 @default.
• W3043103202 cites W2597290376 @default.
• W3043103202 cites W2612547269 @default.
• W3043103202 cites W2742971656 @default.
• W3043103202 cites W2764000436 @default.
• W3043103202 cites W2775790403 @default.
• W3043103202 cites W2790790936 @default.
• W3043103202 cites W2917714624 @default.
• W3043103202 cites W2918028648 @default.
• W3043103202 cites W2938184291 @default.
• W3043103202 cites W2946604129 @default.
• W3043103202 cites W2971243228 @default.
• W3043103202 cites W3009792425 @default.
• W3043103202 cites W3014370651 @default.
• W3043103202 cites W4210441984 @default.
• W3043103202 doi "https://doi.org/10.1165/rcmb.2020-0143oc" @default.
• W3043103202 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7605163" @default.
• W3043103202 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/32668192" @default.
• W3043103202 hasPublicationYear "2020" @default.
• W3043103202 type Work @default.
• W3043103202 sameAs 3043103202 @default.
• W3043103202 citedByCount "36" @default.
• W3043103202 countsByYear W30431032022020 @default.
• W3043103202 countsByYear W30431032022021 @default.
• W3043103202 countsByYear W30431032022022 @default.
• W3043103202 countsByYear W30431032022023 @default.
• W3043103202 crossrefType "journal-article" @default.
• W3043103202 hasAuthorship W3043103202A5009749327 @default.
• W3043103202 hasAuthorship W3043103202A5018496648 @default.
• W3043103202 hasAuthorship W3043103202A5030184709 @default.
• W3043103202 hasAuthorship W3043103202A5042127182 @default.
• W3043103202 hasAuthorship W3043103202A5059656427 @default.
• W3043103202 hasAuthorship W3043103202A5064068796 @default.
• W3043103202 hasAuthorship W3043103202A5066414145 @default.
• W3043103202 hasAuthorship W3043103202A5079814684 @default.
• W3043103202 hasAuthorship W3043103202A5080338987 @default.
• W3043103202 hasAuthorship W3043103202A5083568219 @default.
• W3043103202 hasAuthorship W3043103202A5085995181 @default.
• W3043103202 hasAuthorship W3043103202A5087248857 @default.
• W3043103202 hasBestOaLocation W30431032022 @default.

• next